The cell-surface form of colony-stimulating factor-1 is regulated by osteotropic agents and supports formation of multinucleated osteoclast-like cells.
Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that is released by osteoblasts and is recognized to play a critical role in bone remodeling in vivo and in vitro. CSF-1 is synthesized as a soluble or cell-surface protein. It is unclear, however, whether human osteoblasts express both molecular forms of CSF-1, and whether these isoforms can independently mediate osteoclastogenesis. In the present study, using a combination of quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and Western immunoblot analysis, we have demonstrated that human osteoblast-like cells as well as primary human osteoblasts express the cell-surface form of CSF-1 both constitutively and in response to parathyroid hormone and tumor necrosis factor. Furthermore, using an in vitro co-culture system, we have shown that cell-surface CSF-1 alone is sufficient to support osteoclast formation. These findings may be especially significant in view of evidence that direct cell-to-cell contact is critical for osteoclast formation, and suggest that differential regulation of expression of the CSF-1 isoforms may influence osteoclast function modulated by osteotropic hormones.
Yao
G Q
GQ
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Sun
B h
Bh
Hammond
E E
EE
Spencer
E N
EN
Horowitz
M C
MC
Insogna
K L
KL
Weir
E C
EC
D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006651:Histocytochemistry; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008565:Membrane Proteins; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor